Flavor is a complex mixture of sensory input composed of taste (gustation), smell (olfaction) and the tactile sensation of food as it is being munched, a characteristic that food scientists often term “mouthfeel.” Although people may use the word “taste” to mean “flavor,” in the strict sense it is applicable only to the sensations arising from specialized taste cells in the mouth. Scientists generally describe human taste perception in terms of four qualities: saltiness, sourness, sweetness and bitterness. A fifth taste exists as umami, the sensation elicited by glutamate, one of the 20 amino acids that make up the proteins in meat, fish and legumes. Glutamate also serves as a flavor enhancer in the form of the additive monosodium glutamate (MSG).
Animals use taste systems to evaluate the nutritious value, toxicity, sodium content, and acidity of the food they ingest. In vertebrates, taste reception occurs at the top of the taste cells that form taste buds, and each taste bud has an onion-like shape. There are four major taste areas where taste buds are concentrated; on the tongue at the circumvallate papilla, foliate papilla, and fungiform papilla, and the palate (top of the mouth). Circumvallate papillae, found at the very back of the tongue, contain hundreds to thousands of taste buds. By contrast, foliate papillae, localized to the posterior lateral edge of the tongue, contain dozens to hundreds of taste buds. Further, fungiform papillae, located at the front of the tongue, contain only a single or a few taste buds. Each taste bud, depending on the species, contains 50-150 cells, including precursor cells, support cells, and taste receptor cells (Lindemann et al., 1996, Physiol. Rev. 76:718-66). Receptor cells are innervated at their base by afferent nerve endings that transmit information to the taste centers of the cortex through synapses in the brain stem and thalamus. Elucidating the mechanisms of taste cell signaling and information processing is important to understanding the function, regulation, and perception of the sense of taste.
Much progress has been made in unraveling molecular mechanisms of bitter, sweet and umami taste in recent years (Margolskee, 2002, J. Biol. Chem. 277:1-4; Montmayeur and Matsunami, 2002, Curr. Opin. Neurobiol. 12:366-371; Scott, 2004, Curr. Opin. Neurobiol. 14:423-427). However, the molecular basis of sour taste sensation is the most poorly understood of the five basic modalities.
A whole industry exists around trying to disguise or mask unpleasant tastes. In 1879, Ira Remsen noticed that a derivative of coal tar tasted sweet. H is finding led to the development of saccharin, an artificial sweetener today known as Sweet-n-Low Brand® sweetener. Today, many more artificial sweeteners with varying chemical structures are available including Sunett® (acesulfame potassium), NutraSweet® or Equal®(aspartame), Splenda® (sucralose), and Sugaree® (D-Tagatose). However, some of these artificial sweeteners, such as saccharin and aspartame, have been linked with cancer and other medical problems. Natural plant compounds have also been found to mask unpleasant tastes. Miraculin, a protein found in the pulp of the fruit of the miracle berry, an evergreen shrub native to West Africa, has been described as a “sweet-inducing” protein, and is suggested to bind to sweet taste receptors in the mouth when sour substances are present, the result being a strong sweet taste. Miraculin itself has no distinct taste, but the human tongue when exposed to the protein perceives ordinarily sour foods as sweet. Other plant proteins which are being studied as natural sweeteners include, stevia, curculin, mabinlin, monellin, pentadin, brazzein, and thaumatin (Faus, 2000, Appl. Microbiol. Biotechnol. 53:145-151; Kohmura et al., 2002, Pure Appl. Chem. 74:1235-1242). Contrasted to those individuals who prefer sweet tasting products, there are an equal number who seek out the taste of sour, as evidenced by the myriad of sour candy options available for consumption.
Sweeteners, either artificial or natural, find useful application, for example, as sugar substitutes in the weight loss industry, as sugar alternatives for people suffering from diabetes and other diseases where sugar intake is restricted, as additives to foods and beverages, and in the pharmaceutical industry to make medicaments palatable. Clinically, taste disorders are prevalent in patients undergoing chemotherapy and often have a negative impact on the quality of life and nutrition for those patients. Radiation treatment can also damage taste receptors, giving food a metallic taste. Those patients suffering from taste distortion may avoid foods with high nutritional value, such as fresh fruits and vegetables, thereby further depressing their immune functions. A better understanding of the complex and often multifactorial etiology of taste dysfunction would enable the clinician to institute measures to minimize the impact of these disturbing changes. What is needed is a better understanding of sour taste receptor sensation. What is further needed is a better understanding of sour taste receptor function. Additionally, what is needed are methods and assays to screen for, and to use, ligands that can either inhibit or upregulate sour taste receptor.